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W Lichtenegger

Publications and source records attributed to W Lichtenegger.

At least 19 recordsLinked to original sources
PubMed2006

Biweekly pegylated liposomal doxorubicin in patients with relapsed ovarian cancer: results of a multicenter phase-II trial.

BACKGROUND: The obvious benefit of pegylated liposomal doxorubicin (PLD) for tumour control in recurrent ovarian cancer is frequently offset by severe palmar-plantar erythrodysesthesia (PPE). There is evidence that dose reduction from 50 to 40 mg/m(2) reduces the incidence of PPE without compromising cytotoxic activity. We set out to investigate whether biweekly application further improves the therapeutic index of PLD. PATIENTS AND METHODS: Patients with recurrent ovarian cancer after surgery and adjuvant chemotherapy with platinum and taxane compounds were eligible to participate in this multi-institutional phase II study. PLD was administered at a dose of 20 mg/m(2) every two weeks. Eligible patients had ECOG performance status of < or =2, and sufficient organ function. We employed an optimized two-stage design to test the hypothesis that biweekly application of PLD reduces the frequency of grade III and IV PPE from 25% to 10%. Response and survival were addressed descriptively. RESULTS: Between October 2001 and February 2004, 64 patients with median age of 59 (range 38-81) years were recruited onto this trial. We evaluated 553 (median 7, range 1-25) courses of PLD treatment. Most patients were in their third or fourth line of chemotherapy. PPE was noted in 30 patients (47.6%), but only three participants progressed to grade 3 severity (4.7%, 95% confidence interval 1.0-13.1%). Partial response, stable disease, and tumour progression were observed in 5, 13, and 24 patients, respectively. Median overall and progression-free survival were 18.2 (range, 1.4-34.0) and 4.3 (range 0.5-22.3) months. CONCLUSIONS: Biweekly PLD may reduce the incidence of PPE while retaining efficacy in relapsed ovarian cancer. Our data support the need for a randomized trial to strengthen these assumptions.

Adult↗
PubMed2006

[Breast cancer: analysis of treatment quality in Germany 2004: retrospective survey by Arbeitsgemeinschaft Gynäkologische Onkologie (AGO)].

The Organgruppe Mamma der Arbeitsgemeinschaft Gynaekologische Onkologie (AGO) conducted a nationwide 3-phase analysis of the care structure and standard of therapy given to patients with breast cancer from 2002 (4th quarter) to 2004 (4th quarter). The analysis includes 1069 patients from 257 institutions; 34% with early breast cancer and 66% with metastatic disease. No reliable data on the pattern of care of these patients have been published to date in Germany. The extent to which national and international therapy recommendations were implemented in routine clinical practice was unclear. Evaluation of the data shows that treatment based on the guidelines is now being implemented very reliably in certain sectors. This is of particular relevance to the pattern of adjuvant treatment in early breast cancer. At that time 68 % of the patients received an anthracyclin based chemotherapy and in addition 18% received an anthracycline and taxane based chemotherapy. Participation in clinical trials peaked with 30% in the neoadjuvant setting. The problem with metastatic breast cancer is the complexity of the interdisciplinary treatment involved. The present analysis conducted by the AGO was the first attempt to analyse the treatment given to metastatic patients and to systematise the approach to treatment. The fundamental problem remains, irrespective of the stage of the tumour, namely that too few patients are treated in randomised clinical studies.

Antineoplastic Agents↗
PubMed2006

An estrogen receptor alpha-dependent regulation of estrogen receptor-related receptor alpha in the proliferation of endometrial carcinoma cells.

Estrogen receptor-related receptor alpha (ERRalpha) was reported to compete with estrogen receptor alpha (ERalpha) in a constitutive manner as an orphan nuclear closely related to (ERalpha). To discuss the role of ERRalpha in the endometrial carcinoma cells, this study was performed. ER-responsive endometrial carcinoma cells Ishikawa and ER-nonresponse HEC-1A cells were treated with different concentration of 17beta-E2 or E2 plus ICI 182780. Semiquantitative reverse transcription-polymerase chain reaction and western blot were performed to analysis the expression of human estrogen receptor-related receptor alpha (hERRalpha). Plasmid PLXSN-hERRalpha was constructed and transfected into cells. Selected in the medium containing high-dose G418, the Ishikawa and HEC-1A cells with stable overexpression of hERRalpha were constructed and renamed as Ishikawa/hERRalpha and HEC-1A/hERRalpha, respectively. To discuss the effect of overexpression of hERRalpha in the cell biological behavior (3-[4,5-dimethylth-lazol-2yl]-2,5-diphenyltetrazolium bromid) (MTT) cell assay was performed. Estrogen downregulates ERRalpha expression in ER-positive Ishikawa cells, while upregulates the expression of ERRalpha in ER-negative HEC-1A cells. In Ishikawa cells, the downregulation of 17beta-E2 in ERRalpha expression cells could be blocked by ICI 182780. A decreasing expression of hERalpha was observed in the ER-responsive cells with overexpression of ERRalpha (Ishikawa/hERRalpha). Overexpression of hERRalpha inhibits the cell proliferation in the ERalpha-responsive Ishikawa cells and stimulated the cell proliferation in the ERalpha-nonresponsive HEC-1A cells. Function of hERRalpha depends on the expression and function of hERalpha. ER-mediated signaling might be the important factor resulting in the hormone-dependent endometrial carcinoma, whereas ERRalpha-mediated pathway might act as the vital role in hormone-independent endometrial carcinoma.

Blotting, Western↗
PubMed2005

[Role of PAI-1 in gynaecological malignancies].

The plasminogen activator-plasmin cascade plays a central role in tumor cell invasion and metastasis of solid tumors. The type-1 plasminogen activator inhibitor (PAI-1) is the major physiologic regulator of the plasminogen activation. The PAI-1 is suggested to play a crucial role in tumor cell invasion and metastasis of different solid tumors. The aim of this article is to give an overview of the function, clinical and prognostic role of PAI-1 in gynaecological malignancies.

Female↗
PubMed2004

[Conventional and experimental prognostic factors in ovarian cancer].

Epithelial ovarian cancer is the leading cause of death from gynaecologic malignancies in western countries. In the clinical day treatment decision of the physician (e. g. surgery, chemotherapy) based on individual prognostic factors of the patient with ovarian cancer. The tumor stage at time of diagnosis and the postoperative residual tumor mass are prognostic factors and are unequivocally related to overall survival. Other prognostic factors are identified mostly in small series and are discussed in the literature controversially. This article discussing the value of conventional prognostic factors, as stage, postoperative tumor mass, age, lymph node status, ascites) and newer molecular biological factors, as Her-2-status, PAI-1, MMP, VEGF and CD24.

Biomarkers, Tumor↗
PubMed2004

Dose finding study for combination treatment with topotecan and gemcitabine of patients with recurrent ovarian cancer after failure of first-line chemotherapy with Paclitaxel and platinum.

OBJECTIVES: Topotecan and gemcitabine have shown mono-activity against different solid tumors including recurrent ovarian cancer after failure of platinum- and paclitaxel-containing therapies. Both drugs affect DNA replication, topotecan additionally inhibits the DNA repair process. Efficacy profiles and different mechanisms of action make the combination of both drugs a promising regimen. Therefore the following dose-finding study was conducted to determine the maximum tolerated dose (MTD) and the dose-limiting toxicities (DLT) of this combination. Based on the monotherapy schedules topotecan was given on day 1-5, and gemcitabine on day 1 + 8 every 21 days. PATIENTS AND METHODS: Patients with histologically proven ovarian cancer who relapsed after platinum- and paclitaxel-containing therapy were enrolled. 3 different dose levels were investigated. No individual dose escalation or primary use of cytokines were allowed. RESULTS: 23 patients were enrolled, 50% were pretreated with at least 2 platinum-containing therapies; 80 courses were analyzed for toxicity. Thrombocytopenia and leucopenia were the major DLTs. The MTD for phase II trials is 0.50 mg/m(2) topotecan and 800/600 mg/m(2) gemcitabine. In this dose level only one therapy-related non-hematological adverse event >grade 2 (grade 3 mycotic stomatitis) and one grade 4 thrombocytopenia occurred. Responses were observed in 6 and stable disease in 4 out of 12 evaluable patients. Median survival was 15.3 (95% CI: 13.2-28.6) months. CONCLUSIONS: The results of this phase I study demonstrate the feasibility and tolerability of this new combination in heavily pretreated patients. Based on these results a phase II study was initiated to evaluate the efficacy of this regimen.

Adult↗
PubMed2003

Interleukin-1 receptor antagonist gene polymorphism is associated with increased risk of epithelial ovarian cancer.

BACKGROUND: Different studies indicate that immunological components play a key role in the development of cancer. Interleukin-1 (IL-1) is known to be critically involved in ovarian carcinogenesis and in other solid tumors. Therefore, we investigated the possible influence of the polymorphism of the IL-1 receptor antagonist (IL-1 RA) genes on the development of ovarian cancer. PATIENTS AND METHODS: In a prospective study we analyzed the polymorphism of the IL-1 RA gene in 108 women with ovarian cancer compared with 112 patients with benign gynecological diseases. Genomic DNA fragments were amplified by PCR. RESULTS: The distribution of genotype frequencies was significantly different between the study and control group with respect to allele 1/2 heterozygotes (32.4% versus 15.2%; P = 0.004). Patients who were heterozygous at allele 2 for IL-1 RA (IL-RA 1/2) had a significantly higher risk of ovarian cancer with a calculated odds ratio of 2.7 (95% confidence interval 1.4-5.2). There were no differences between IL-1 RA 1/2 polymorphism and all other alleles in tumor stage (International Federation of Gynecology and Obstetrics), histological type, grading, postoperative tumor volume, volume of ascites, recurrence status or age. CONCLUSIONS: The allele 2 polymorphism of the IL-1 RA gene seems to play a role in the occurrence of ovarian cancer and should be investigated for screening and risk evaluation.

Adult↗
PubMed2002

A phase II study of topotecan plus gemcitabine in the treatment of patients with relapsed ovarian cancer after failure of first-line chemotherapy.

BACKGROUND: Second-line chemotherapy for patients with ovarian cancer who failed platinum and paclitaxel treatment remains a therapeutic challenge. We investigated the toxicity profile and therapeutic efficacy of a novel combination regimen, topotecan plus gemcitabine, in a clinical phase II study. PATIENTS AND METHODS: Women with relapsed epithelial ovarian cancer after platinum and paclitaxel treatment were eligible to participate in this trial. Topotecan was given at an initial dose of 0.5 mg/m(2) daily (days 1-5), combined with gemcitabine 800 mg/m(2) and 600 mg/m(2) on days 1 and 8, respectively. Precluding good tolerability, this protocol facilitated subsequent dose increases of topotecan up to 1.0 mg/m(2). The primary objective was to determine the dose-limiting toxicity, whereas secondary objectives comprised measurable and CA-125 response rates, disease-free and overall survival. RESULTS: The twenty-one patients (median age 57 years, range 37-70 years) who were allocated to this trial received a total of 94 courses of chemotherapy. Median follow-up was 20.5 months. Topotecan dosage could be escalated to 0.75 mg/m(2) in nine patients and 1 mg/m(2) in another two patients. Dose reduction was not necessary in any case. There were no episodes of neutropenic fever, sepsis or chemotherapy-related fatalities. Only one patient developed CTC grade 4 leukopenia after the first treatment cycle, whereas three patients showed grade 3/4 anaemia. Five patients experienced thrombocytopenia grade 4 without clinical sequelae. Non-hematological toxicities were mild and rare. Eleven patients could be evaluated for clinical tumour response, with three complete, and four partial remissions. Two patients each had stable and progressive diseases. The median progression-free survival rate was 8.8 months [95% confidence interval (CI) 6.3-13.4 months]. The median overall survival rate was 21.1 months (95% CI 14.8-22.1 months). CONCLUSIONS: Topotecan combined with gemcitabine has a favourable toxicity profile and encouraging efficacy in patients with recurrent ovarian cancer.

Adult↗
PubMed2001

[Adjuvant chemotherapy of cervix carcinoma--results of a phase II study].

OBJECTIVE: Therapies involving a radical operation and radiation treatment for cervical carcinoma in stages I and II are not sufficiently effective in patient subgroups with high risk for recurrence. In recent publications, patients with high risk cervical cancer had with adjuvant simultaneous radio-chemotherapy a better disease free and overall survival but a higher toxicity compared with patients received an adjuvant radiotherapy alone. MATERIAL AND METHODS: 34 patients with at least 2 risk factors for recurrence of cervical cancer were treated with adjuvant chemotherapy after radical hysterectomy. The protocol consisted of 3 cycles of ifosfamide 1.6 g/m2 (d 1-3) and carboplatin (AUC 4, d1) every three weeks. For cell protection 21 patients received amifostine 740 mg/m2 d1-3; this was followed by standard radiation therapy (50.4 Gy percutaneous and high-dose-rate-after-loading for 21 patients, 2 x 5 Gy). The dose determination of the substances and their toxicity were investigated. RESULTS: Patient (p) data: Median age 43 years (range: 25-70); pT1b-2a: n = 22; pT2b: n = 12; pN1: n = 28; pN0: n = 6; G3: n = 10; adeno- and adenosquamous carcinoma: n = 9, G3: n = 10, R1-resection: n = 5. 70.6% of these high-risk patients were disease-free after a median observation time of 40 (18-62) months. Median number of cycles of chemotherapy: 2.8. There was no more dose escalation than carboplatin according to AUC 4 possible. Hematologic toxicity (CTC grading, % of 96 documented cycles): anemia-grade 3-4: 30; -grade 1-2: 10.4; leukopenia-grade 3-4: 13, -grade 1-2: 21.7; alopecia-grade 3: all p.; cerebral neurotoxicity-grade 3-4: 8.3, -grade 1-2; 17.7; diarrhea under radiotherapy-grade 3-4: 2 p., -grade 1-2: 6 p. CONCLUSION: This combined sequential adjuvant therapy was effective and had an acceptable level of toxicity. A phase III study comparing adjuvant sequential chemo-radiotherapy with and without Erythropoeitin to counteract the negative effects of anemia started in Germany in 1999 and had randomized now about 270 patients.

Adenocarcinoma↗
PubMed2001

Risk perception and psychological strain in women with a family history of breast cancer.

BACKGROUND: The thinking in health psychology is that patients' willingness to adopt preventive health behavior is contingent on their perceiving an increased risk of disease and is influenced by accompanying psychological stress. In counseling women with a family history of breast cancer, physicians focus on encouraging the patient to undergo early detection examinations as recommended. Therefore, it is essential to examine how women in this risk group perceive their own chances of developing breast cancer and to assess the psychological effects of their situation. MATERIAL AND METHODS: 129 women with at least one first or second degree relative who had developed breast cancer were enrolled in a questionnaire study. The object was to ascertain the extent to which these women may be expected to realistically estimate their own probability of contracting the disease and what influence risk perception and psychological strain have on their willingness to make use of diagnostic opportunities for early detection. Additionally, the effects on their physical and mental well-being were analyzed. RESULTS: Among the women of the study group, a family history of breast cancer did not always correlate with the subject's perception of an increased risk of contracting the disease compared. On the whole, the majority of the women overestimated their personal risk despite prior genetic counseling. Only slightly less than one quarter of the study group correctly estimated their risk; another quarter underestimated it. The majority of those women who exhibited an increased risk perception were also those who overestimated their probability of personally contracting the disease. They underwent recommended screening examinations significantly less often than women with a low risk perception. However, women subjected to intense psychological strain showed above-average participation in screening programs. CONCLUSIONS: Women with a family history of breast cancer often find it difficult to realistically estimate their own risk of contracting the disease. Increased risk perception had a negative effect on participation in recommended breast cancer screening. Therefore, an effort should be made to correct the patient's overestimation of her personal risk. Integrating psychological counseling in screening programs is essential considering that women from high-risk groups are subjected to increased psychological strain. Further studies are required to more precisely evaluate other psychosocial factors in the behavior of women in risk group toward screening.

Adult↗
PubMed2001

Correlation of p53 mutations with resistance to platinum-based chemotherapy and shortened survival in ovarian cancer.

PURPOSE: The p53 tumor suppressor gene plays a central role in cell cycle regulation and induction of apoptosis. We analyzed p53 alterations and their impact on response to chemotherapy and clinical outcome in ovarian cancer patients. EXPERIMENTAL DESIGN: One hundred seventy-eight ovarian carcinomas, snap frozen and stored at -80 degrees C, were analyzed for mutations of the p53 gene (exons 2-11) by single-strand conformation polymorphism and DNA sequencing and for p53 overexpression by immunohistochemistry (monoclonal antibody DO7). RESULTS: p53 mutations were found in 56% (99 of 178) of the tumors, and 62% of these were located in evolutionary highly conserved domains of the gene. Time to progression and overall survival were significantly shortened in patients with p53 mutations compared with wild-type p53 (P = 0.029 and P = 0.014) and patients with mutations in highly conserved domains as opposed to nonconserved domains or wild-type p53 (P = 0.010 and P = 0.007). p53 protein overexpression (>10% positively stained nuclei) was found in 62% (110 of 178). Time to progression and overall survival were shorter in cases with p53 overexpression (cutpoint, 10%: P = 0.071 and P = 0.056) but only marginally significant. Resistance to adjuvant cisplatin or carboplatin chemotherapy was significantly more frequent in patients with p53 overexpression (P = 0.001) or p53 missense mutations (P = 0.008) than patients with normal p53. CONCLUSIONS: p53 alterations correlate significantly with resistance to platinum-based chemotherapy, early relapse, and shortened overall survival in ovarian cancer patients in univariate analysis. In multivariable analysis though, p53 was not an independent prognostic factor.

Aged↗
PubMed2000

p21 (WAF1/CIP1) protein expression is associated with prolonged survival but not with p53 expression in epithelial ovarian carcinoma.

OBJECTIVE: The objective of this study was to clarify the influence of p21 protein expression in ovarian cancer. p21 (WAF1 [wild-type p53 activated fragment 1]/CIP1) is a universal cyclin-dependent kinase inhibitor and can be induced as a downstream effector of the p53 tumor suppressor gene. METHODS: The expression of p21 was evaluated by immunohistochemical analysis with the monoclonal antibody WAF1 (Oncogene Science) on 106 formalin-fixed, paraffin-embedded tissue samples of epithelial ovarian cancer. RESULTS: p21 was expressed in 65 (61%) of all cases. p21 expression was associated with early stage in FIGO classification (FIGO I and II, P = 0.003) and no tumor residues after primary tumor resection (P = 0.018). Immunohistochemical staining results were judged as negative if no tumor nuclei were stained, as weak positive if 1-49% were stained, and as strong positive if over 50% of nuclei were stained. Clinical follow-up showed a better overall survival for cases with strong p21 expression (79 months) versus 40 months for weak expression and 30 months for no expression (P = 0.033). Previously determined p53 expression of this cohort was compared with p21 status. p53 overexpression was observed in 49 cases (48%) and showed no association with p21 expression. CONCLUSION: No correlation was found between p21 and p53 expression. p21 expression is a significant prognostic marker for improved survival in ovarian cancer and is associated with early FIGO stage and zero tumor residues after primary tumor resection.

Adult↗
PubMed2000

Nitroglycerin application during cesarean delivery: plasma levels, fetal/maternal ratio of nitroglycerin, and effects in newborns.

OBJECTIVE: We sought to investigate maternal and fetal nitroglycerin metabolization and to assess the clinical condition of neonates after intravenous nitroglycerin application during cesarean delivery. STUDY DESIGN: At the time of the uterine puncture incision, either 0. 25 mg or 0.5 mg nitroglycerin or a physiologic sodium chloride solution was administered as an intravenous bolus. Plasma concentrations of nitroglycerin and its metabolites were measured in maternal venous blood and in umbilical blood samples taken immediately after cord clamping. Arterial blood pressure, pulse rates, and Apgar scores were recorded for the neonates 1, 5, and 10 minutes after birth. RESULTS: Sixty-two patients were included in the pharmacokinetic study. Median maternal plasma levels 1 and 5 minutes after injection of 0.5 mg nitroglycerin were 80 and 3.2 ng/mL, respectively; median maternal plasma levels 1 and 5 minutes after injection of 0.25 mg nitroglycerin were 38 and 1.2 ng/mL, respectively. In the umbilical vein 1 minute after application of 0. 5 mg or 0.25 mg nitroglycerin, the plasma levels were 0.41 and 0.09 ng/mL, respectively, and in the umbilical artery they were 0.03 and 0.008 ng/mL, respectively. Circulatory parameters and Apgar scores in the neonates did not differ significantly from those found in the placebo group. CONCLUSION: The level of nitroglycerin in umbilical plasma was two to three orders of magnitude lower than that found in maternal plasma and clearly in a subtherapeutic range. There was no indication that prenatal application of nitroglycerin to facilitate obstetric management is hazardous for neonates.

Adolescent↗
PubMed2000

Primary mucinous adenocarcinoma of the appendix: a rare entity in the differential diagnosis of ovarian cancer.

We report a 58-year-old female patient with the suspected diagnosis of ovarian cancer. Upon surgical exploration, examination of the appendix revealed the histological diagnosis of primary mucinous adenocarcinoma. This is an unusual consideration in the differential diagnosis of the ovarian cancer. We discuss the diagnosis, classification and treatment of the cancer of the appendix in relation to ovarian cancer.

Adenocarcinoma, Mucinous↗
PubMed2000

Comparison of the relaxation effect in vitro of nitroglycerin vs. fenoterol on human myometrial strips.

AIMS: Substance dose-related comparison of relaxation effect of nitroglycerin (GTN) and the beta 2-mimetic substance fenoterol in human myometrial tissue. METHODS: Test criterion is the isometric force development of isolated human myometrial strips. These muscle strips were removed from the lower uterine segment at cesarean section. Fenoterol in concentrations of 3 x 10(-8)-10(-5) mol/l or GTN in concentrations of 1.7 x 10(-8)-5.8 x 10(-4) mol/l were applied to the 2 x 2 x 10-mm strips, which were fixed and maintained in tissue baths. The curves were plotted on line. The integral or the "area under the curve" (AUC) served as the parameter for muscle strip activity. RESULTS: A total of 100 strips from 20 patients were used. GTN demonstrated a significant relaxation effect in the in vitro model on human myometrial strips from pregnant women already treated with oxytocin. The effect was able to be enhanced to a point where oxytocin-induced contractions were completely absent. A relatively clear connection was demonstrated between dose and effect whereby increased muscle relaxation resulted at increased concentrations. Compared to GTN application, muscle strip relaxation was less pronounced under fenoterol; a complete inhibition of myometrial activity was not achieved under fenoterol. CONCLUSIONS: With respect to relaxation of the myometrial tissue samples the NO donor GTN is at least as potent as the standard tocolytic agent fenoterol in the in vitro model.

Adrenergic beta-Agonists↗
PubMed2000

Pre-operative staging of cervical cancer: comparison of magnetic resonance imaging (MRI) and computed tomography (CT) with histologic results.

Thirty-two patients with histologically confirmed cervical carcinoma were preoperatively investigated using MRI; in addition, a CAT-scan was performed on 15 of these patients. The diagnostic results using both modalities were compared with the histological findings (after hysterectomy according to Wertheim-Meigs, including lymph node dissection in the pelvic and, in part, in para-aortal regions). Determination of tumour volume was possible with high accuracy using MRI. Accuracy in assessing the parametria was 86%, vagina 90%, bladder and rectum 97%. The shortcoming of MRI is still the detection of infiltrated lymph nodes. The accuracy of 69% achieved for lymph nodes is equal to results with computed tomography. The general accuracy for our patients in staging was 81% for MRI versus 47% for CT. MRI-based diagnosis enables us to determine a correct tumour staging preoperatively, and is therefore very helpful in planning an adequate therapy. If MRI were used more widely it would contribute to simplification and shortening of the preoperative diagnostic procedure in patients with cervical carcinoma.

Adult↗